The Extracytoplasmic Function Sigma Factor σ S Protects against both Intracellular and Extracytoplasmic Stresses in Staphylococcus aureus

Previously we identified a novel component of theStaphylococcus aureus regulatory network, ane xtrac ytoplasmicf unction σ-factor, σS , involved in stress response and disease causation. Here we present additional characterization of σS , demonstrating a role for it in protection against DNA damage, cell wall disruption, and interaction with components of the innate immune system. Promoter mapping reveals the existence of three uniquesigS start sites, one of which appears to be subject to autoregulation. Transcriptional profiling revealed thatsigS expression remains low in a number ofS. aureus wild types but is upregulated in the highly mutated strain RN4220. Further analysis demonstrates thatsigS expression is inducible upon exposure to a variety of chemical stressors that elicit DNA damage, including methyl methanesulfonate and ciprofloxacin, as well as those that disrupt cell wall stability, such as ampicillin and oxacillin. Significantly, expression ofsigS is highly induced during growth in serum and upon phagocytosis by RAW 264.7 murine macrophage-like cells. Phenotypically, σS mutants display sensitivity to a broad range of DNA-damaging agents and cell wall-targeting antibiotics. Furthermore, the survivability of σS mutants is strongly impacted during challenge by components of the innate immune system. Collectively, our data suggest that σS likely serves dual functions within theS. aureus cell, protecting against both cytoplasmic and extracytoplasmic stresses. This further argues for its important, and perhaps novel, role in theS. aureus stress and virulence responses.